MOODSTRATIFICATION IMMUNOSTRATA Groningen
Premature immune ageing to predict the effect of physical training intervention
in mood disorders

Physical training intervention is hypothesized to alleviate signs of premature
aging of the immune system in mood disorder (MD) patients and has concomitantly
beneficial effects on the depression severity.

The premature immune aging state can predict treatment response to physical
training.
Therefore, MD patients with the most outspoken premature immune aging (i.e.
those with signs in the highest tertile) respond better than those with weak or
absent premature immune aging (i.e. those with signs in the lowest tertile).

The signs used for the definition of premature immune aging are:
1. an increased monocyte apoptotic/SASP gene expression (or a correlate thereof
in a whole blood preparation),
2. a positive CMV antibody status
3. reduced serum levels of IL-7
4. increased serum levels of hsCRP and IL-6.

Primary objective:
To assess whether the state of premature immune aging (senescent CD8+ T cells)
predicts treatment response to physical endurance intervention therapy in
depressed patients. We will compare the mood-beneficial effects of physical
endurance training in all depressed patients and in those with high versus
those with low signs of premature aging of the immune system.

Secondary objectives:
To compare the longer term socio-economic beneficial effects of physical
endurance training in all depressed patients and those with high versus those
with low signs of premature aging of the immune system.
To compare the signs of a premature aging of the immune system before and after
physical endurance training in mood disorder patients.
To assess whether the state of chronic inflammation indeed predicts treatment
response to TAU with first-line antidepressants (serotonergic/noradrenergic) in
depressed patients as it did in our previous studies and in the literature. We
will therefore compare the mood-beneficial effects of the first line TAU drugs
in all depressed patients and in those with
a) high versus low levels of hsCRP,
b) high versus low levels of IL-6,
c) high versus low levels of pro-inflammatory monocytes and leukocytes.
To construct easy and clinical applicable (finger prick) assay to measure
immune senescence and chronic inflammation in depressed patients

We will include 2 groups in this study to assess the role of exercise training
on the immune system in MD. The MD patients will be randomized into 2 groups:
Treatment as usual (TAU) and TAU combined with exercise training.

Participants in group 1 will receive treatment as usual (TAU), i.e.
pharmacotherapy plus clinical management.

Participants in group 2 will receive TAU combined with exercise training,
consisting of a cycling exercise. The participants in the exercise groups will
do a cycling exercise of 30 minutes, 3 times every week, during a period of 8
weeks.
In the training program, the Functional Threshold Power (measured with
ergometry) will be used to choose the optimal heart rate range for each
patient. The intensity level will increase from 45-50% to 50-60% in the second
week, to 60-65% in the third week and up to 65-70% from the fifth week on.
These increases are necessary to ensure a high enough intensity.

Burden
Baseline measurement (including interview, questionnaires, blooddraw,
ergometry) for patients will take approximately 120 minutes.
End of treatment measurement (including questionnaires, blooddraw, ergometry))
for patients will take approximately 90 minutes.
The follow op meeting for patients will take approximately 60 minutes.
The physical training intervention, for half of the patients, will take 35
minutes, 3 times per week, during 8 weeks.

Risks
We do not expect major safety problems related to the study parameters. During
the blood sample drawing and fitness test qualified study personal will be
present. As the study is conducted in the hospital, participants can receive
medical attention if required.

Benefit
The study provides no benefits for the participating participants.